Targeting strategy for gene delivery to carcinoembryonic antigen-producing cancer cells by retrovirus displaying a single-chain variable fragment antibody.
Cancer-specific antigens are promising targets for the specific delivery of certain drugs or genes to cancer cells in cancer therapy. Carcinoembryonic antigen (CEA) is one of the cancer-associated antigens predominantly detected in the gastrointestinal cancer of the colon and stomach. Targeting strategies for CEA-producing cancer cells have been thoroughly developed mainly by the production of monoclonal antibodies to CEA and further single-chain variable fragment (scFv) antibodies. Here, we have generated Moloney murine leukemia virus-derived retroviral vectors co-displaying an anti-CEA scFv-envelope chimeric protein and an unmodified envelope protein to deliver a gene for herpes simplex virus thymidine kinase (HSV-tk) or Escherichia coli beta-galactosidase. The harvested viruses successfully incorporated the chimeric envelope protein as well as the unmodified envelope into the viral particles, and specifically bound to and infected human CEA-producing cancer cells via recognition of CEA, depending on the CEA-producing phenotype of the target cells. These results may have significant implications for the use of scFv directed against tumor-specific antigens for targeting specific antigen-producing cancer cells, a potential step toward in vivo cancer therapy.
Konishi
H
H
First Department of Surgery, National Cancer Center Research Institute, University of Tokyo, Japan.
Ochiya
T
T
Chester
K A
KA
Begent
R H
RH
Muto
T
T
Sugimura
T
T
Terada
M
M
Begent
R H
RH
D016475:3T3 Cells; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis* / Q000235:genetics*; D005770:Gastrointestinal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000138:chemical synthesis; D006367:HeLa Cells; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000235:genetics; D019065:Virus Assembly / Q000235:genetics
D002272:Carcinoembryonic Antigen; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D014759:Viral Envelope Proteins